We undertook a phase Ib study of recombinant human granulocyte macrophage colony stimulating factor (GM-CSF) to determine not only the ability of this agent to stimulate myelopoiesis in vivo but also for its ability to stimulate functional activity of mature hematopoietic cells. GM-CSF was given in a dose escalation manner to consecutive groups of three patients with doses ranging from 1 up to 50 micrograms per kilogram daily. Toxic effects included fatigue, bone pain, nausea, myalgias, and headaches. Occasional patients developed rash, diarrhea, and chills. At the highest dose administered, hypotension, decreased serum albumin levels, and increased serum alkaline phosphatase levels were observed. Treatments resulted in dose-related increases in white blood cell and granulocyte counts, eosinophilia, and slight increases in monocytes and lymphocyte counts. All counts return rapidly to normal following discontinuation of treatments. There was enhancement of HLA-DR expression on peripheral blood monocytes but decreased expression of Fc receptor expression on these same cells. There was increased expression of CDllB (an adhesion molecule) on the surface of the granulocytes. There was no direct enhancement of monocyte or granulocyte function as measured by tumoricidal activity or superoxide generation respectively. Thus, although this agent had significant effects on myelopoiesis and activated monocytes as determined by HLA-DR expression, the agent itself appears to be incapable of enhancing tumoricidal activity of monocytes or granulocytes. If this agent is to be used as a tumoricidal agent, it must be coupled with an agent capable of stimulating functional activity of granulocytes and monocytes.